Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 279, Issue 1, Pages 219-222Publisher
ACADEMIC PRESS INC
DOI: 10.1006/bbrc.2000.3906
Keywords
callipeltin A; cardiac Na+/Ca2+ exchanger; guinea pig atria; positive inotropic effect
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Callipeltin A, a cyclic depsipeptide from the New Caledonian Lithistida sponge Callipelta sp., is a macrocyclic lactone containing four amino acids in the L configuration, Ala, Leu, Thr (2 residues); one (Arg) in the D configuration; two N-methyl amino acids, N-MeAla and N-MeGln; a methoxy tyrosine, a 3,4-dimethyl-L-glutamine; and a 4-amino-7-guanidino-2,3 dihydroxypentanoic acid (AC;DHE), formally derived from L-Arg. In cardiac sarcolemmal vesicles Callipeltin A induces a powerful (IC50 = 0.85 muM) and selective inhibition of the Na+/Ca2+ exchanger. In electrically driven guinea-pig atria, at concentrations ranging between 0.7 and 2.5 muM, Callipeltin A induces a positive inotropic effect, which at the highest concentrations is accompanied by a rise in resting tension. It is suggested that the positive inotropic effect is linked to the inhibition of the Na+/Ca2+ exchanger and that Callipeltin A may be an useful tool to study the role of the cardiac Na+/Ca2+ exchanger in physiological and pathological conditions. (C) 2000 Academic Press.
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